Type 2 Diabetes MellitusPhase 1NCT02223065

Bioequivalence Study Coadministered to Healthy Subjects in the Fasted State

A Phase 1 study testing Saxagliptin and Dapagliflozin in people with Type 2 Diabetes Mellitus, run by AstraZeneca.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to demonstrate bioequivalence of coadministered drugs on healthy subjects. Read more about this study

Who is it for?: Ages 19 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Saxagliptin and Dapagliflozin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: No sites listed yet
Study dates: Sep 2014to Dec 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 19 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.
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.
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

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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.
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.
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

Who cannot join

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.

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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
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.
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.
Glucosuria or hematoria at screening or Day -1 of Period 1, repeat is not permitted. d) A positive nicotine test (ie, cotinine).
Abnormal liver function tests (alanine or aspartate aminotransferase [ALT or AST, respectively], or total bilirubin).
Any of the following on 12-lead ECG prior to study drug administration, confirmed by repeat.
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.
Allergies and Adverse Drug Reaction
History of allergy or adverse reactions to DPP4 or SGLT inhibitors or related compounds.
History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
Other Exclusion Criteria
Prisoners or subjects who are involuntarily incarcerated.
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Inability to comply with restrictions and prohibited activities/treatments

About this study

Official 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

The purpose of this study is to demonstrate bioequivalence of coadministered drugs on healthy subjects.

Conditions: Type 2 Diabetes Mellitus
Being tested: Saxagliptin, Dapagliflozin
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SaxagliptinDrug
Also called Onglyza
DapagliflozinDrug
Also called Farxiga in the United States, Forxiga in other countries

Study groups in NCT02223065
Study group	Role	What they receive
Treatment A	Experimental	Single oral dose of saxagliptin tablet coadministered with dapagliflozin tablet Receives: Drug: Saxagliptin; Drug: Dapagliflozin
Treatment B	Experimental	Single oral dose of FDC (fixed-dose combination) tablet Receives: Drug: Saxagliptin; Drug: Dapagliflozin

What is being measured

The primary outcome is the main question the study is designed to answer.

Saxagliptin Maximum Observed Concentrations (Cmax)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Measured: Day 1-3 (Period 1) and Day 8-10 (Period 2)
Dapagliflozin Maximum Observed Concentrations (Cmax)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Measured: Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2)
Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Measured: Day 1-3 (Period 1) and Day 8-10 (Period 2)
Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Measured: Day 1-3 (Period 1) and Day 8-10 (Period 2)
Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Measured: Day 1-3 (Period 1) and Day 8-10 (Period 2)
Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Measured: Day 1-3 (Period 1) and Day 8-10 (Period 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2014Dec 2014

First posted22 Aug 2014 (estimated)
Study startSep 2014
Primary completionDec 2014
Study completionDec 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02223065
Sponsor's protocol ID: CV181-364
Status last verified: Mar 2016
First submitted: 19 Aug 2014
Last updated: 27 Apr 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
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Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
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Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
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Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official 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
ClinicalTrials.gov ID: NCT02223065
Acronym / sponsor ID: CV181-364
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Sep 2014
Primary completion: Dec 2014 (actual)
Study completion: Dec 2014 (actual)
First posted: 22 Aug 2014 (estimated)
Results: Posted 27 Apr 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to demonstrate bioequivalence of coadministered drugs on healthy subjects.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Treatment A	Experimental	Drug: Saxagliptin, Drug: DapagliflozinSingle oral dose of saxagliptin tablet coadministered with dapagliflozin tablet
Treatment B	Experimental	Drug: Saxagliptin, Drug: DapagliflozinSingle oral dose of FDC (fixed-dose combination) tablet

Who may qualify

Ages: 19 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (10 listed)

Signed Informed Consent Form
Target Population
Age and Reproductive Status

Key exclusion criteria (28 listed)

Physical and Laboratory Test Findings
Allergies and Adverse Drug Reaction
Other Exclusion Criteria

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SaxagliptinAlso: Onglyza	Drug	Treatment A, Treatment B
DapagliflozinAlso: Farxiga in the United States, Forxiga in other countries	Drug	Treatment A, Treatment B

Primary outcome

Saxagliptin Maximum Observed Concentrations (Cmax)
Time frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Dapagliflozin Maximum Observed Concentrations (Cmax)
Time frame: Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
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)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
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)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
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)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
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)
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Results and safety

Results posted to the registry on 27 Apr 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment AB	18	18
Treatment BA	18	18

Primary outcome: Saxagliptin Maximum Observed Concentrations (Cmax)

Time frame: Day 1-3 (Period 1) and Day 8-10 (Period 2). Geometric mean (90% Confidence Interval). Unit: ng/mL

Measure	Treatment A n = 36	Treatment B n = 36
Value	26.2 (5.723)	25.5 (5.763)

Treatment A vs Treatment B: Geometric mean ratio: 0.975 (90% CI 0.915 to 1.038), p = 0.4950, ANOVA

Population analysed: Evaluable PK Population

Primary outcome: Dapagliflozin Maximum Observed Concentrations (Cmax)

Time frame: Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2). Geometric mean (90% Confidence Interval). Unit: ng/mL

Measure	Treatment A n = 36	Treatment B n = 36
Value	142 (28.93)	141 (37.10)

Treatment A vs Treatment B: Geometric mean ratio: 0.993 (90% CI 0.932 to 1.060), p = 0.8650, ANOVA

Population analysed: Evaluable PK Population

Primary outcome: 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). Geometric mean (90% Confidence Interval). Unit: ng.h/mL

Measure	Treatment A n = 36	Treatment B n = 36
Value	95.9 (5.723)	98.0 (5.763)

Treatment A vs Treatment B: Geometric mean ratio: 1.022 (90% CI 0.991 to 1.054), p = 0.2344, ANOVA

Population analysed: Evaluable PK Population

Primary outcome: 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). Geometric mean (90% Confidence Interval). Unit: ng.h/mL

Measure	Treatment A n = 36	Treatment B n = 36
Value	537 (5.723)	546 (5.763)

Treatment A vs Treatment B: Geometric mean ratio: 1.016 (90% CI 0.993 to 1.038), p = 0.2458, ANOVA

Population analysed: Evaluable PK Population

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment A	0 of 36 (0%)	0 of 36 (0%)	Not reported
Treatment B	0 of 36 (0%)	0 of 36 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Type 2 Diabetes Mellitus

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Not yet recruitingPhase 3
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Not yet recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael Gartner, MD principal investigator

Celerion

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Saxagliptin and Dapagliflozin in people with Type 2 Diabetes Mellitus, run by AstraZeneca.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Saxagliptin Maximum Observed Concentrations (Cmax) (time frame: Day 1-3 (Period 1) and Day 8-10 (Period 2)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02223065.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2016.