A Study to Assess the Bioequivalence of Dapagliflozin/Metformin XR Fixed-dose Combination Tablets in Healthy Subjects

NCT02637037 | Completed Phase 1 Results

• 1 other identifier: D1691C00008
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Bioequivalence; Fixed Dose Combination Tablets; Healthy Male and Female Subjects

Keywords

dapagliflozin/metformin XR 5/500 mg; dapagliflozin/metformin XR10/1000 mg; bioequivalence; fixed dose combination tablets; pharmacokinetic; type 2 Diabetes Mellitus (T2DM); safety

Outcome Measures

Primary Outcomes (3)

• Area Under Plasma Concentration-time Curve [AUC] Under Fasted or Fed State

  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.

  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

  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 Outcomes (4)

• Time to Reach Maximum Plasma Concentration (t Max)

  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]

  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]

  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]

  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

Study Arms (8)

Treatment A

EXPERIMENTAL

Under fed conditions, subjects will receive single doses of dapagliflozin/metformin XR test drug (Mount Vernon) 5/500 mg dose

Drug: dapagliflozin/metformin XR 5/500 mg test drug (Mount Vernon)

Treatment B

ACTIVE COMPARATOR

Under fed conditions, subjects will receive single doses of dapagliflozin/metformin XR reference drug (Humacao) 5/500 mg dose

Drug: dapagliflozin/metformin XR 5/500 mg reference drug (Humacao)

Treatment C

EXPERIMENTAL

Under fasted conditions, subjects will receive single doses of dapagliflozin/metformin XR test drug (Mount Vernon) 5/500 mg dose

Drug: dapagliflozin/metformin XR 5/500 mg test drug (Mount Vernon)

Treatment D

ACTIVE COMPARATOR

Under fasted conditions, subjects will receive single doses of dapagliflozin/metformin XR reference drug (Humacao) 5/500 mg dose

Drug: dapagliflozin/metformin XR 5/500 mg reference drug (Humacao)

Treatment E

EXPERIMENTAL

Under fed conditions, subjects will receive single doses of dapagliflozin/metformin XR test drug (Mount Vernon) 10/1000 mg dose

Drug: dapagliflozin/metformin XR 10/1000 mg test drug (Mount Vernon)

Treatment F

ACTIVE COMPARATOR

Under fed conditions, subjects will receive single doses of dapagliflozin/metformin XR reference drug (Humacao) 10/1000 mg dose

Drug: dapagliflozin/metformin XR 10/1000 mg reference drug (Humacao)

Treatment G

EXPERIMENTAL

Under fasted conditions, subjects will receive single doses of dapagliflozin/metformin XR test drug (Mount Vernon) 10/1000 mg dose

Drug: dapagliflozin/metformin XR 10/1000 mg test drug (Mount Vernon)

Treatment H

ACTIVE COMPARATOR

Under fasted conditions, subjects will receive single doses of dapagliflozin/metformin XR reference drug (Humacao) 10/1000 mg dose

Drug: dapagliflozin/metformin XR 10/1000 mg reference drug (Humacao)

Interventions

dapagliflozin/metformin XR 5/500 mg test drug (Mount Vernon) DRUG

single fixed-combination dose tablets

Treatment A; Treatment C

dapagliflozin/metformin XR 5/500 mg reference drug (Humacao) DRUG

single fixed-dose combination tablets

Treatment B; Treatment D

dapagliflozin/metformin XR 10/1000 mg test drug (Mount Vernon) DRUG

single fixed-dose combination tablets

Treatment E; Treatment G

dapagliflozin/metformin XR 10/1000 mg reference drug (Humacao) DRUG

single fixed-dose combination tablets

Treatment F; Treatment H

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin; Drug Evaluation

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic

Results Point of Contact

• Title: Global Clinical Leader
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

+46 31 7761000

Study Officials

• Ronald Goldwater, MDCM, M.Sc, CPI

  PAREXEL Early Phase Clinical Unit Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 22, 2015
• Study Start: December 21, 2015
• Primary Completion: April 7, 2016
• Study Completion: April 7, 2016
• Last Updated: March 13, 2018
• Results First Posted: March 13, 2018

Record last verified: 2018-03

Locations

US (1)