- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02637037
A Study to Assess the Bioequivalence of Dapagliflozin/Metformin XR Fixed-dose Combination Tablets in Healthy Subjects
March 11, 2018 updated by: AstraZeneca
A Two Part Bioequivalence Study to Compare Two Fixed Dose Combination Tablets of Dapagliflozin/Metformin XR 5/500 mg (Part 1) and 10/1000 mg (Part 2) Manufactured at Two Different Plants in Healthy Subjects Under Fasting and Fed Conditions
This is a bioequivalence study to compare 2 fixed-dose combination tablets of dapagliflozin/metformin XR manufactured at 2 different plants in healthy subjects under fasting and fed conditions
Study Overview
Status
Completed
Detailed Description
This is a Phase 1, 2-part, open-label, randomized, 4-period, 4-treatment, crossover study in healthy subjects (males and females of non-childbearing potential)
Study Type
Interventional
Enrollment (Actual)
80
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21225
- Research Site
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 53 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Provision of signed and dated, written informed consent prior to any study specific procedures
- Healthy male and female subjects aged 18 - 55 years with suitable veins for cannulation or repeated venipuncture
Females must have a negative serum pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:
- Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post-menopausal range
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation
- Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive at screening
Exclusion Criteria:
- History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product
- Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the investigator
- Any clinically significant abnormal findings in vital signs, as judged by the investigator
- Any clinically significant abnormalities on 12-lead ECG as judged by the investigator
- Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody
- Known or suspected history of drug abuse, as judged by the investigator
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose.
- Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to dapagliflozin/metformin XR.
- Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening
- Positive screen for drugs of abuse, cotinine or alcohol at screening or on each admission to the study center
- Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, vitamins and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life
- Known or suspected history of alcohol abuse or excessive intake of alcohol as judged by the investigator
- Involvement of any AstraZeneca or study site employee or their close relatives
- Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment A
Under fed conditions, subjects will receive single doses of dapagliflozin/metformin XR test drug (Mount Vernon) 5/500 mg dose
|
single fixed-combination dose tablets
|
Active Comparator: Treatment B
Under fed conditions, subjects will receive single doses of dapagliflozin/metformin XR reference drug (Humacao) 5/500 mg dose
|
single fixed-dose combination tablets
|
Experimental: Treatment C
Under fasted conditions, subjects will receive single doses of dapagliflozin/metformin XR test drug (Mount Vernon) 5/500 mg dose
|
single fixed-combination dose tablets
|
Active Comparator: Treatment D
Under fasted conditions, subjects will receive single doses of dapagliflozin/metformin XR reference drug (Humacao) 5/500 mg dose
|
single fixed-dose combination tablets
|
Experimental: Treatment E
Under fed conditions, subjects will receive single doses of dapagliflozin/metformin XR test drug (Mount Vernon) 10/1000 mg dose
|
single fixed-dose combination tablets
|
Active Comparator: Treatment F
Under fed conditions, subjects will receive single doses of dapagliflozin/metformin XR reference drug (Humacao) 10/1000 mg dose
|
single fixed-dose combination tablets
|
Experimental: Treatment G
Under fasted conditions, subjects will receive single doses of dapagliflozin/metformin XR test drug (Mount Vernon) 10/1000 mg dose
|
single fixed-dose combination tablets
|
Active Comparator: Treatment H
Under fasted conditions, subjects will receive single doses of dapagliflozin/metformin XR reference drug (Humacao) 10/1000 mg dose
|
single fixed-dose combination tablets
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under Plasma Concentration-time Curve [AUC] Under Fasted or Fed State
Time Frame: Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
To evaluate the Bioequivalence for Dapagliflozin and Metformin following administration Dapagliflozin/Metformin XR 5/500 mg and 10/1000 mg Manufactured at Mt. Vernon plant, US, Compared to Humacao plant, Puerto Rico, in the Fasted or Fed state.
|
Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
AUC From Time Zero to Time of Last Quantifiable Concentration [AUC (0-t)] Under Fasted or Fed State.
Time Frame: Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
To evaluate the Bioequivalence for Dapagliflozin and Metformin following administration Dapagliflozin/Metformin XR 5/500 mg and 10/1000 mg Manufactured at Mt. Vernon plant, US, Compared to Humacao plant, Puerto Rico, in the Fasted or Fed state
|
Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
Observed Maximum Plasma Concentration [Cmax] Under Fasted or Fed State
Time Frame: Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
To evaluate the Bioequivalence for Dapagliflozin and Metformin following administration Dapagliflozin/Metformin XR 5/500 mg and 10/1000 mg Manufactured at Mt. Vernon plant, US, Compared to Humacao plant, Puerto Rico, in the Fasted or Fed state
|
Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Reach Maximum Plasma Concentration (t Max)
Time Frame: Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
To characterize and compare the pharmacokinetic profiles of dapagliflozin and metformin when administered as the 2 fixed-dose combination formulations and in the fed and fasted states.
|
Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve [t½λz]
Time Frame: Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
To characterize and compare the pharmacokinetic profiles of dapagliflozin and metformin when administered as the 2 fixed-dose combination formulations and in the fed and fasted states.
|
Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC [CL/F]
Time Frame: Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
To characterize and compare the pharmacokinetic profiles of dapagliflozin and metformin when administered as the 2 fixed-dose combination formulations and in the fed and fasted states.
|
Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration [Vz/F]
Time Frame: Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
To characterize and compare the pharmacokinetic profiles of dapagliflozin and metformin when administered as the 2 fixed-dose combination formulations and in the fed and fasted states.
|
Days 1 to 3: pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose for each treatment period
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Ronald Goldwater, MDCM, M.Sc, CPI, PAREXEL Early Phase Clinical Unit Baltimore
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 21, 2015
Primary Completion (Actual)
April 7, 2016
Study Completion (Actual)
April 7, 2016
Study Registration Dates
First Submitted
December 15, 2015
First Submitted That Met QC Criteria
December 18, 2015
First Posted (Estimate)
December 22, 2015
Study Record Updates
Last Update Posted (Actual)
March 13, 2018
Last Update Submitted That Met QC Criteria
March 11, 2018
Last Verified
March 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- D1691C00008
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Bioequivalence
-
Pharmtechnology LLCRecruitingBioequivalenceRussian Federation
-
Emzor Pharmaceutical Industries LimitedNot yet recruiting
-
Pharmtechnology LLCClinPharmInvest, LLCNot yet recruitingBioequivalenceRussian Federation
-
Indiana UniversityFood and Drug Administration (FDA)Completed
-
AstraZenecaCompletedBioequivalenceUnited States
-
Future University in EgyptCompleted
-
Cross Research S.A.Zambon SpACompleted
-
Laboratorios Andromaco S.A.Completed
-
Emzor Pharmaceutical Industries LimitedUnknown
-
Jiangsu HengRui Medicine Co., Ltd.Unknown
Clinical Trials on dapagliflozin/metformin XR 5/500 mg test drug (Mount Vernon)
-
AstraZenecaCompleted
-
AstraZenecaCompletedHealthy Subjects in Fasted and Fed StateBrazil
-
AstraZenecaCompleted
-
Shandong Suncadia Medicine Co., Ltd.Not yet recruiting
-
AstraZenecaParexelCompletedType 2 Diabetes MellitusUnited States
-
AstraZenecaBristol-Myers SquibbCompletedType 2 Diabetes Mellitus(T2DM)China
-
Dong-A ST Co., Ltd.Completed
-
Dexa Medica GroupCompletedMetformin XR BE Study in Healthy Volunteers With Single and Multiple DoseIndonesia
-
Woman'sAstraZenecaCompletedDapagliflozin and Metformin,Alone and in Combination, in Overweight/Obese Prior GDM Women (DAPA-GDM)Diabetes Prevention in Women After GDM Who Are at High-riskUnited States
-
The University of Texas Health Science Center at...AstraZenecaCompletedDiabetes Mellitus, Type 2United States