A Bioequivalence Study of a Randomized, Open-label, Single Dose, Two-way Crossover Design With Two-period, Two-treatment and Two-sequence of Dapagliflozin Tablet 10 mg Relative to Forxiga® in Healthy Thai Volunteers Under Fasting Condition
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Bio-innova Co., Ltd
- Enrollment
- 30
- Primary Endpoint
- Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC 0-t)
Study Overview
Brief Summary
The study is to compare the rate and extent of absorption of a generic formulation with that of a reference for mulation when given as equal labeled dose. The study will be randomized, open-label, single dose, two way crossover design with two-period, two-treatment and two-sequence under fasting condition and at least 5 days washout period between the doses.
Detailed Description
Title A Bioequivalence study of a randomized, open-label, single dose, two-way crossover design with two-period, two-treatment and two-sequence of Dapagliflozin tablet 10 mg relative to Forxiga® film-coated tablets 10 mg, of AstraZeneca pharmaceuticals LP, Mount Vernon, Indiana, USA in healthy Thai volunteers under fasting condition
Objectives The primary objective is to compare the rate and extent of absorption of a generic formulation with that of a reference formulation when given as equal labeled dose. The secondary objective is to evaluate the safety after oral administration of both test and reference formulation in healthy Thai volunteers.
Study Design Randomized, open-label, single dose, two-way crossover design with two-period, two-treatment and two-sequence under fasting condition and at least 5 days washout period between the doses.
Sample Size 30 Healthy Human Thai subjects. Two extra subjects if available, may be checked-in on the day of check in of period-I to compensate for any dropout prior to dosing of period-I. These subjects will be dosed if there are dropouts prior to dosing in period-I. If there are no dropouts, these subjects will be checked-out without being dosed after completion of dosing in period-I.
Drug-Product Test-Product: Dapagliflozin tablet 10 mg Reference-product: FORXIGA® (10 MG FILM-COATED TABLETS) Manufactured by: ASTRAZENECA PHARMACEUTICALS LP, USA
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Willingness to provide written informed consent prior to participate in the study.
- •Healthy Thai subjects are between 18 to 55 years of age.
- •The Body Mass Index (BMI) ranges from 18.5 to 30 kg/m
- •Comprehensive of the nature and purpose of the study and compliance with the requirement of the entire protocol and allow investigators to draw 7 mL of blood for monitoring subjects' safety after the completion of the study.
- •Negative urine pregnancy test for women and no breast-feeding.
- •Absence of significant diseases or clinically significant abnormal laboratory values on the laboratory evaluations, medical history or surgery during the screening. Some of the laboratory values e.g. Complete blood count etc. that out of the normal range will be carefully considered by physician.
Exclusion Criteria
- •History or evidence of allergy or hypersensitivity to Dapagliflozin or any related drugs or any of the excipients of this product.
- •Subject with B.P. is Systolic B.P < 90, ≥140 mm/Hg, Diastolic B.P < 60, ≥90 mm/Hg, pulse rate > 100 beats per minute.
- •Serum bilirubin greater than 1.5 times the upper limit of reference range (ULRR).*
- •Serum creatinine greater than 1.5 times the upper limit of reference range (ULRR).*
- •Alanine amino transferase (ALT) or aspartate amino transferase (AST) greater than 2 times the upper limit of reference range (ULRR).*
- •Positive of hepatitis B or C virus or HIV.
- •Have more than one abnormal EKG, which is considered as clinically significant. *
- •History or evidence of heart, renal, hepatic disease, pulmonary obstructive disease, bronchial asthma, hypertension or glaucoma
- •History or evidence of gastrointestinal disorder likely to influence drug absorption or previous GI surgery other than appendectomy.
- •Any major illness in the past 3 months or any significant ongoing chronic medical illness.
- •History that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause or severe starvation within 1 month before drug administration.
- •History of psychiatric disorder.
- •History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) and cannot stop at least 2 days before the study drug administration and until the completion of each period of the study.
- •History of usually smoking (more than 10 cigarettes per day within past 1 year), if moderate smokers (less than 10 cigarettes per day) cannot stop at least 7 days before the study drug administration and until the completion of the study.
- •High caffeine consumption (more than 5 cups of coffee or tea per day) and cannot stop at least 2 days before the study drug administration and until the completion of each period of the study.
- •Positive drug abused test in urine (Benzodiazepines, Marijuana (THC), Methamphetamine, Cocaine and Opioids).
- •Receipt of any prescription drug therapy within 14 days or 5 half-lives (whichever longer) preceding the first dose of study medication or over-the-counter (OTC) drugs or herbal medicines/food supplement within 7 days or hormonal methods of contraception within 28 days (Depo-Provera must be discontinued at least 6 months) prior to the study drug administration.
- •History of difficulty in accessibility of veins in left and right arm.
- •Blood donation (one unit or 450 mL) within the past 3 months before the study.
- •Participation in any clinical study within the past 3 months before the study.
- •Subjects who are unwilling or unable to comply with the lifestyle guidelines described in this protocol.
- •(* Depend on decision of principal investigator and/or clinical investigator)
Arms & Interventions
Sequence 1- Dapagliflozin test product and then reference product
Participants will receive treatment 1 in period 1 and treatment 2 in period 2. Where treatment 1= Dapagliflozin tablet 10 mg test product, treatment 2= Dapagliflozin tablet 10 mg reference product.
Intervention: Dapagliflozin-Test product (Drug)
Sequence 2-Dapagliflozin reference product and then test product
Participants will receive treatment 2 in period 1 and treatment 1 in period 2. Where treatment 1= Dapagliflozin tablet 10 mg test product, treatment 2= Dapagliflozin tablet 10 mg reference product.
Intervention: Dapagliflozin-Reference product (Drug)
Outcomes
Primary Outcomes
Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC 0-t)
Time Frame: Blood samples will be collected for PK analyses in each period pre-dose (0.00 hour) and at 0.25, 0.50, 0.75, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00 and 48.00 hours post-dose
pre-dose (0.00 hour) and at 0.25, 0.50, 0.75, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00 and 48.00 hours post-dose
Maximal measured plasma concentration (Cmax)
Time Frame: Blood samples will be collected for PK analyses in each period pre-dose (0.00 hour) and at 0.25, 0.50, 0.75, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00 and 48.00 hours post-dose
pre-dose (0.00 hour) and at 0.25, 0.50, 0.75, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 6.00, 8.00, 12.00, 16.00, 24.00 and 48.00 hours post-dose
Secondary Outcomes
- Number of subjects with adverse events(Approximately the day 14 after the last visit)
Investigators
Sasitorn Kittivoravitkul
Principal Investigator
Bio-innova Co., Ltd