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Healthy VolunteerPhase 1NCT04856007

A Study to Assess the Bioequivalence of Fixed Dose Combination of Dapagliflozin/Metformin XR Relative to Co-administration of the Individual Components in Healthy Chinese Subjects.

A Phase 1 study testing Dapagliflozin/metformin XR FDC 5/500 mg, Dapagliflozin/metformin XR FDC 10/1000 mg and Dapagliflozin 5 mg + Metformin 500 mg XR in people with Healthy Volunteer, run by AstraZeneca at 1 site in China.

Completed

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

Official record
Search all trials

Trial summary

To assess the bioequivalence between dapagliflozin/metformin XR FDC tablet and co-administration of dapagliflozin and metformin XR tablets. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Volunteer
What is being tested?
Dapagliflozin/metformin XR FDC 5/500 mg, Dapagliflozin/metformin XR FDC 10/1000 mg and Dapagliflozin 5 mg + Metformin 500 mg XR
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteChina
Study dates
12 Apr 2021to 14 Jun 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Provision of informed consent prior to any study specific procedures.
  • Healthy Chinese subjects as determined by no clinically significant deviation from normal in medical history, vital signs, physical examination, 12-lead ECG, and clinical laboratory evaluations.
  • Male or female, ages 18 to 55 years, inclusive, at the time of signing the informed consent
  • Weigh at least 50 kg (for male) and 45 kg (for female), respectively, and have a body mass index (BMI) ≥ 19 and <26 kg/m2. BMI = weight (kg)/[height (m)]2.
  • Female participants: Women of childbearing potential must use one highly effective form of birth control.
  • Must be able to communicate with the investigator, understand and comply with all study requirements.

Who cannot join

  • Any significant acute or chronic medical illness.
  • Current or recent (within 3 months prior to study drug administration) gastrointestinal disease that may impact drug absorption and affect PK of the study drugs. Additionally, any gastrointestinal surgery (eg, partial gastrectomy, pyloroplasty) that could impact the absorption of study drug.
  • Any major surgery, as determined by the investigator, within 4 weeks prior to study drug administration.
  • Donation of blood within 3 months prior to study drug administration.
  • Blood transfusion within 4 weeks prior to study drug administration.
  • Inability to tolerate oral medication.
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  • Inability to tolerate venous access.
  • Drug or alcohol abuse within 6 months prior to study drug administration. Alcohol abuse is defined as a history of regular alcohol consumption exceeding 14 drinks per week, or a positive breath alcohol test at screening and/or check-in. 1 drink equals to 5 ounces (150ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of hard liquor.
  • Regularly drink more than 3 cups of coffee or other caffeine-containing products a day, or 5 cups of tea a day.
  • Regular smoker (the subject should be able to abstain from smoking for the duration of the study without having abstinence, therefore they should not be regular smokers, regular smokers are defined as people who smoke everyday), use of tobacco-containing or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 4 weeks prior to study drug administration .
  • Any other sound medical, psychiatric and/or social reason as determined by the investigator.
  • Any of the following on ECG prior to study drug administration:
  • PR≥210ms
  • QRS≥120ms
  • QT≥500ms
  • QTcF≥450ms(male) or QTcF≥470ms(female)
  • Positive urine screen for drugs of abuse.
  • Any clinically significant abnormal findings in urinalysis (may repeat once) at screening, as judged by the investigator.
  • Glucosuria at screening.
  • Abnormal liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or total bilirubin > 10% above upper limit of normal [ULN]).
  • Elevated serum creatinine (> ULN).
  • Positive blood screen for HIV antibody , Syphilis antibody, hepatitis C antibody , or Hepatitis B surface antigen (HbsAg) or only Hepatitis B core antibody (anti-HBc) in Hepatitis B serologic test.
  • History of allergy to SGLT2 inhibitor drug class or related compounds.
  • History of allergy or intolerance to metformin or other similar acting agents.
  • History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
  • Prior exposure to metformin or dapagliflozin within 3 months of study drug administration.
  • Exposure to any investigational product or placebo within 4 weeks prior to study drug administration.
  • Use of any prescription drugs or over-the counter (OTC), traditional Chinese medicine and herbal preparations within 4 weeks prior to study drug administration.
  • Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff or staff at the study site).
  • Previous enrolled or randomized in the present study.
  • For women only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding.
  • Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
  • Has clinical signs and symptoms consistent with COVID-19 infection (eg fever, dry cough, dyspnea, sore throat, fatigue.. etc) as judged by investigator or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
  • History of COVID-19.

Trial locations and contacts

1 site in 1 country.

China1 site
  • Research Site

    Suzhou, 215006

Other trials in China

About this study

Official title: A Single-centre, Parallel-cohort, Randomized, Open-label, Two-period, Cross-over, Bioequivalence Study of the Fixed Dose Combination of Dapagliflozin/Metformin XR Relative to Co-administration of the Individual Components in Two Cohorts of Healthy Chinese Subjects in the Fed State.

To assess the bioequivalence between dapagliflozin/metformin XR FDC tablet and co-administration of dapagliflozin and metformin XR tablets.

Read the detailed description

A Single-centre, Parallel-cohort, Randomized, Open-label, Two-period, Cross-over, Bioequivalence Study of the Fixed Dose Combination of Dapagliflozin/Metformin XR Relative to Co-administration of the Individual Components in Two Cohorts of Healthy Chinese Subjects in the Fed State.

Being tested
Dapagliflozin/metformin XR FDC 5/500 mg, Dapagliflozin/metformin XR FDC 10/1000 mg, Dapagliflozin 5 mg + Metformin 500 mg XR, Dapagliflozin 10 mg + Metformin 1000 mg XR
Keywords
Dapagliflozin, Forxiga, Metformin XR, Glucophage XR, Xigduo XR, Bioequivalence, Cross-over

What participants receive

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

  • Dapagliflozin/metformin XR FDC 5/500 mgDrug

    Also called Xigduo XR

    In cohort 1, subjects will be randomized to receive co-administration of a single oral dose of a 5mg dapagliflozin tablet and a 500mg metformin XR tablets (Treatment A) followed by 7 to 14 days washout and then receive single FDC tablet consisting of 5mg dapagliflozin and 500mg metformin XR (Treatment B) on Day 1 in one treatment sequence. Or subjects will be randomized to be administered the Treatment B followed by 7 to 14 days washout and then received Treatment A on Day1 in the other treatment sequence.

  • Dapagliflozin/metformin XR FDC 10/1000 mgDrug

    Also called Xigduo XR

    In cohort 2, subjects will be randomized to receive co-administration of a single oral dose of a 10mg dapagliflozin tablet and two 500mg metformin XR tablets (Treatment C) followed by 7 to 14 days washout and then receive single FDC tablet consisting of 10mg dapagliflozin and 1000mg metformin XR (Treatment D) on Day 1 in one treatment sequence. Or subjects will be randomized to be administered the Treatment D followed by 7 to 14 days washout and then received Treatment C on Day1 in the other treatment sequence.

  • Dapagliflozin 5 mg + Metformin 500 mg XRDrug

    Also called Forxiga + Glucophage XR

    In cohort 1, subjects will be randomized to receive co-administration of a single oral dose of a 5mg dapagliflozin tablet and a 500mg metformin XR tablets (Treatment A) followed by 7 to 14 days washout and then receive single FDC tablet consisting of 5mg dapagliflozin and 500mg metformin XR (Treatment B) on Day 1 in one treatment sequence. Or subjects will be randomized to be administered the Treatment B followed by 7 to 14 days washout and then received Treatment A on Day1 in the other treatment sequence.

  • Dapagliflozin 10 mg + Metformin 1000 mg XRDrug

    Also called Forxiga + Glucophage XR

    In cohort 2, subjects will be randomized to receive co-administration of a single oral dose of a 10mg dapagliflozin tablet and two 500mg metformin XR tablets (Treatment C) followed by 7 to 14 days washout and then receive single FDC tablet consisting of 10mg dapagliflozin and 1000mg metformin XR (Treatment D) on Day 1 in one treatment sequence. Or subjects will be randomized to be administered the Treatment D followed by 7 to 14 days washout and then received Treatment C on Day1 in the other treatment sequence.

Study groups in NCT04856007
Study groupRoleWhat they receive
Dapagliflozin 5mg + Metformin 500mg XRExperimentalco-administration of a single oral dose of a 5mg dapagliflozin (Forxiga® 5mg) tablet and a 500mg metformin XR (Glucophage XR®) tablet
Receives: Drug: Dapagliflozin/metformin XR FDC 5/500 mg
Dapagliflozin/metformin XR FDC 5/500 mgExperimentalsingle FDC tablet consisting of 5mg dapagliflozin and 500mg metformin XR subject
Receives: Drug: Dapagliflozin 5 mg + Metformin 500 mg XR
Dapagliflozin 10mg + Metformin 1000mg XRExperimentalco-administration of a single oral dose of a 10mg dapagliflozin (Forxiga® 10mg) tablet and two 500mg metformin XR (Glucophage XR®) tablets
Receives: Drug: Dapagliflozin/metformin XR FDC 10/1000 mg
Dapagliflozin/metformin XR FDC 10/1000 mgExperimentalingle FDC tablet consisting of 10mg dapagliflozin and 1000mg metformin XR
Receives: Drug: Dapagliflozin 10 mg + Metformin 1000 mg XR

What is being measured

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

  1. Area under the plasma concentration-time curve from zero to the last quantifiable concentration(AUClast) of dapagliflozin and metformin.

    For period 1 and 2, PK samples will be collected pre-dose and 0.5,1,2,3,4,6,8,10,12,24(Day2),36,48(Day3), and 72(Day4) hours post dose.

    Measured: From Day 1 to Day 4, in Treatment period 1 and 2, respectively. An average of 11 to 18 days.

  2. Area under the plasma concentration-time curve from zero to infinity (AUCinf) of dapagliflozin and metformin.

    For period 1 and 2, PK samples will be collected pre-dose and 0.5,1,2,3,4,6,8,10,12,24(Day2),36,48(Day3), and 72(Day4) hours post dose.

    Measured: From Day 1 to Day 4, in Treatment period 1 and 2, respectively. An average of 11 to 18 days.

  3. Maximum observed plasma concentration (Cmax) of dapagliflozin and metformin.

    For period 1 and 2, PK samples will be collected pre-dose and 0.5,1,2,3,4,6,8,10,12,24(Day2),36,48(Day3), and 72(Day4) hours post dose.

    Measured: From Day 1 to Day 4, in Treatment period 1 and 2, respectively. An average of 11 to 18 days.

Secondary outcomes (5)
  1. Time to maximum observed plasma concentration (tmax) of dapagliflozin and metformin.

    For period 1 and 2, PK samples will be collected pre-dose and 0.5,1,2,3,4,6,8,10,12,24(Day2),36,48(Day3), and 72(Day4) hours post dose.

    Measured: From Day 1 to Day 4, in Treatment period 1 and 2, respectively. An average of 11 to 18 days.

  2. Terminal elimination rate constant (λz) of dapagliflozin and metformin.

    For period 1 and 2, PK samples will be collected pre-dose and 0.5,1,2,3,4,6,8,10,12,24(Day2),36,48(Day3), and 72(Day4) hours post dose.

    Measured: From Day 1 to Day 4, in Treatment period 1 and 2, respectively. An average of 11 to 18 days.

  3. Half-life associated with terminal slope of a semi-logarithmic concentration-time curve(t½λz) of dapagliflozin and metformin.

    For period 1 and 2, PK samples will be collected pre-dose and 0.5,1,2,3,4,6,8,10,12,24(Day2),36,48(Day3), and 72(Day4) hours post dose.

    Measured: From Day 1 to Day 4, in Treatment period 1 and 2, respectively. An average of 11 to 18 days.

  4. Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of dapagliflozin and metformin.

    For period 1 and 2, PK samples will be collected pre-dose and 0.5,1,2,3,4,6,8,10,12,24(Day2),36,48(Day3), and 72(Day4) hours post dose.

    Measured: From Day 1 to Day 4, in Treatment period 1 and 2, respectively. An average of 11 to 18 days.

  5. Apparent volume of distribution following extravascular administration (Vz/F) of dapagliflozin and metformin.

    For period 1 and 2, PK samples will be collected pre-dose and 0.5,1,2,3,4,6,8,10,12,24(Day2),36,48(Day3), and 72(Day4) hours post dose.

    Measured: From Day 1 to Day 4, in Treatment period 1 and 2, respectively. An average of 11 to 18 days.

Timeline

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

  1. First posted22 Apr 2021
  2. Study start12 Apr 2021
  3. Primary completion14 Jun 2021
  4. Study completion14 Jun 2021

Resources

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
Other
Allocation
Randomised
Intervention model
Crossover
Model description
There will be two independent cohorts of subjects who will each receive two treatments in a randomized order, and each treatment will be followed by 72 hours of blood sampling for pharmacokinetic assessments, with safety and tolerability. In each cohort approximately 40 healthy subjects will be randomized to receive treatment with IP in order to complete at least 36 evaluable subjects.
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04856007
Sponsor's protocol ID
D1691C00011
Status last verified
Apr 2022
First submitted
9 Apr 2021
Last updated
29 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Publications

  • Zhao X, Ning R, Hui A, Boulton DW, Tang W. Pharmacokinetic Variables of Dapagliflozin/Metformin Extended-release Fixed-dose Combination in Healthy Chinese Volunteers and Regional Comparison. Clin Ther. 2023 Aug;45(8):762-769. doi: 10.1016/j.clinthera.2023.06.012. Epub 2023 Jul 11.

    PubMed 37442656

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dapagliflozin/metformin XR FDC 5/500 mg, Dapagliflozin/metformin XR FDC 10/1000 mg and Dapagliflozin 5 mg + Metformin 500 mg XR in people with Healthy Volunteer, run by AstraZeneca at 1 site in China.

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 6 inclusion and 34 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 29 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Area under the plasma concentration-time curve from zero to the last quantifiable concentration(AUClast) of dapagliflozin and metformin. (time frame: From Day 1 to Day 4, in Treatment period 1 and 2, respectively. An average of 11 to 18 days.). The study lists 3 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 NCT04856007, which also lists 1 linked publication.

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 29 Apr 2022.

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